Sandbox 81

Alpha Lactalbumin
α-lactalbumin is a small acidic protein present in all kinds of milk studied thus far. α- lactalbumin contributes to cell lytic activity, cell growth inhibition, and apoptosis but most importantly, it interacts with UDP-galactosyltransferase to form lactose synthetase via the following reaction:

UDP-galactose + glucose -+ lactose + UDP

which takes place in the Golgi lumen and requires Mn2+ ions.

Structure
α-lactalbumin is a small globular protein, with 123 residues,, with two structural domains divided by a deep cleft. One domain is rich in α-helices and held together by two disulfide bonds, Cys 6-Cys 120 and Cys 28-Cys 111. It is made up of three major helices (residues 5-11, 23-24,and 86-98)and 2 short 3-10 helices (residues 18-20, and 115-118). The other has a small three-stranded antiparallel beta-pleated sheet (residues 41-44, 47-50, and 55-56), a short 3-10 alpha-helix (residues 77-80), and two disulfide bonds, Cys 61-Cys 77 and Cys 73-Cys 91. The domains are held together by a calcium binding loop formed by a cysteine bridge between residues 73 and 91, and also a disulfide bridge between residues 61 and 77. .

The secondary structure has nine alpha helices shown as pink rockets, and two beta sheets shown as yellow planks. The four disulfide bonds are shown by the yellow strings. It also has three strands, and 2 beta hairpins, and 11 beta turns.

The side chains are shown here with nonpolar side chains in gray, polar side chains in purple, and associated water molecules in red. The hydrophobic side chains congregate in the center of the protein with the polar side chains on the periphery. The water molecules are associated with the polar side chains.

Here are shown the polar uncharged residues with the cations in blue, the anions in red, hydrophobic residues in gray, polar uncharged residues in light purple, and the backbone residues in dark purple.

In the beta-rich domain there are two calcium binding sites, shown here are the calcium ligands with their amino acid contacts (water molecules are shown in pink and oxygen molecules are shown in red). The first site, the primary site is made of three asparagine side chains and two carbonyls, and has a pentagonal bypyramidal coordination with active sites: LYS A 79  ASP A  82  ASP A  84  ASP A  87 ASP A  88. The second site has a tetrahedral coordination with active sites: THR A 38  GLN A  39  LEU A  81  ASP A  83.

Recent Studies
Tryptophan is a component of alpha-lactalbumin proteins, the availability of which changes the ratio of plasma tryptophan to the sum of larger neutral amino acids (Trp-LNAA ratio). Tryptophan is a serotonin precursor and proper serotonin function in the brain has been shown to promote sleep regulation and cognitive processes. Deficient serotonin function, possibly from chronic stress, can result in difficulty sleeping and therefore behavioral decline. Recent studies have shown that consumption of alpha-lactalbumin protein with enriched tryptophan content caused increased alertness and performance the morning after.

Many studies have found that infants who are formula- fed have different growth and amino acid patterns from breast-fed infants from the lack of alpha-lactalbumin. The addition of bovine alpha-lactalbumin to formula makes the growth and plasma amino acid patterns of formula-fed infants more similar to those of breast-fed infants, and improves their growth. HAMLET (human alpha-lactalbumin made lethal to tumor cells) is the topic of much recent study. Alpha-lactalbumin is converted into a folding variant with altered biological function which can induce apoptosis in tumor and premature cells, healthy cells are resistant to this. For HAMLET to form partial unfolding needs to occur, as well as the presence of C18:1, a fatty acid. The studies have shown that HAMLET may help lower cancer in breast-fed infants by killing the tumor cells in their stomachs because the low pH releases Ca21 from the binding site and activates lipases that hydrolyze free fatty acids from milk triglycerides.